Endometrial Transcriptome Changes following Short-Term Liraglutide Treatment in Infertile Women with Polycystic Ovarian Syndrome and Obesity.

Abstract

Objectives: The aim of the study was to evaluate whether the use of a 12-week liraglutide treatment changes the endometrial gene expression during the implantation window in infertile obese women with polycystic ovarian syndrome (PCOS) undergoing in vitro fertilization (IVF).

Design: A cross-sectional study involving treated and non-treated subjects was conducted.

Participants: Infertile women with PCOS and BMI ≥30 kg/m2 participated in the study.

Setting: The study was conducted at a tertiary-care university hospital.

Methods: Endometrial biopsies were collected from 20 infertile women during the implantation window, 1 month prior to entering the IVF procedure. Endometrium transcriptome of 10 participants, who had been pretreated with low-dose liraglutide 1.2 mg QD for 12 weeks and achieved at least a 5% reduction in body weight, was compared to endometrium transcriptome of 10 treatment-naive participants, who had a stable body weight over the last 12 weeks. Next-generation sequencing was conducted to analyze RNA from the samples. The resulting data were processed to discern key canonical pathways and predict activations or inhibitions. Gene networks were constructed based on established published associations.

Results: Gene Set Analysis (GSA) identified a total of 17 canonical pathways that were significantly differentially expressed between the two groups. The most important canonical pathways included GLP-1 receptor activation, modulation of inflammation and oxidative stress response, alterations in glucose homeostasis, and energy consumption, with YWHAG being a notable central gene in the associated network. The results indicate a possible involvement of the AKT pathway in the liraglutide mode of action.

Limitations: The main limitations include its cross-sectional design and considerable number of upregulated and downregulated genes.

Conclusions: Short-term low-dose liraglutide treatment prior to IVF was associated with changes in the endometrial transcriptome that could potentially be important for improving endometrial receptivity and fertility in women with obesity and PCOS.